cardiopulmonary exercise testing to evaluate pulmonary avms

Conditions: Pulmonary Arteriovenous Malformations; Hereditary Hemorrhagic Telangiectasia

Summary: pulmonary arteriovenous malformations (pavms) are a rare vascular condition affecting the lungs. pavms lead to low blood oxygen levels, yet are very well tolerated by patients. this study will examine the exercise capacity of pavm patients using formal cardiopulmonary exercise tests performed on a stationary bicycle.

it is well known that the lung is the site at which oxygen enters the blood stream, diffusing from the alveolar air sacs into the pulmonary capillaries. this newly oxygenated blood is carried to the heart in the pulmonary veins, then passes into the systemic circulation to provide oxygen to the tissues. patients with pulmonary arteriovenous malformations (pavms) have abnormal vascular connections between pulmonary arteries and pulmonary veins in the lung. blood flowing through pavms therefore bypasses the oxygenation sites in the pulmonary capillaries. low blood oxygen levels (hypoxemia) is frequent in pavm patients but breathlessness (dyspnea) is not. the investigators have shown that dyspnea was not a common presenting complaint in a large uk series, and that there is little correlation between severity of dyspnea in pavm patients, and blood oxygen levels. in this study the investigators will address the question "why are hypoxemic pavm patients not more dyspneic?" the investigators will address this by first performing standardised cardiopulmonary exercise testing, as used in the clinic, on age and sex matched patients with pavms and healthy controls. physiological parameters will be compared, to test the null hypothesis that the impact of exercise on pavm patients' cardiopulmonary systems does not differ to normal controls. if the expected differences are confirmed, the investigators will examine if there is any difference to normals by re-examining the exercise tolerance of the pavm cohort after they have had their pavms treated by embolization. most patients with pavms have an underlying hereditary vascular disorder, hereditary haemorrhagic telangiectasia. assuming the expected differences between pavm patients and controls are confirmed, the investigators will therefore also examine which pattern hht patients without pavms display. finally, cellular and molecular methods will be used to dissect mechanistic pathways.

Eligibility criteria:
inclusion criteria: * ability to provide informed consent * healthy volunteers: no concurrent health reason to avoid exercise * pulmonary avms: pulmonary avms confirmed by ct scan * hereditary hemorrhagic telangiectasia without pulmonary avms: hht according to current international consensus criteria, with no evidence of pavms on dedicated thoracic ct scan. exclusion criteria: * inability to provide informed consent. * any known cardiovascular abnormality including a history of syncope (faintness, dizziness, lightheadedness or loss of consciousness due to an abnormality of the cardiovascular system). * current respiratory tract infection (eg a cold). * pregnancy. * claustrophobia or needle phobia

Keywords: workload oxygen level oxygen consumption breathing reserve ventilatory efficiency